In this ongoing research program, we endeavor to elucidate molecular interactions between the coagulation, fibrinolytic, kinin forming and complement system. We are exploring the capacity of defined reaction products of these systems to activate, regulate or to injure cellular elements such as platelets, endothelial cells, mast cells, lymphocytes and polymorphonuclear leukocytes. We are studying intermolecular and molecule-cell interactions in isolated systems, to identify biologically active molecules and to delineate their structural and immunochemical properties. We have come to appreciate the essential role that surfaces play in the assembly and activation of certain multimolecular functional units. Antibody molecules are being used as probes to delineate functional sites and neoantigenic determinants in the native and (patho)physiologically altered molecules of the coagulation and complement system. The molecular and biochemical information thus accumulated is being applied to the study of disease models and clinical disease. The study of disseminated intravascular coagulation occupies a central position in the program and almost all individual projects contribute to it. In this supplemental application we propose to pursue new findings made in the course of the above work, and to apply new biochemical information and methodology to the study of disseminated intravascular coagulation. The biophysics and biochemistry of human Factors XII, XI and IX will be pursued and the interaction of these proteins with platelets will be studied. The fate of coagulation factors in experimental disseminated intravascular coagulation in the rabbit will be determined, including molecular size changes of Factor VIII. The structural properties of specific markers on fibrinolytic peptides will be elucidated and the pathobiological consequences of autoantibody production to these peptides in disease will be explored. In toto this work will aid elucidation of the molecular and cellular events underlying the occurrence of thrombosis and the pathogenesis of blood vessel injury in man.